A Trial of GH001 in Patients With Treatment-resistant Depression

NCT05800860 | Completed Phase 2

• 2 other identifiers: GH001-TRD-2012022-000574-26
• Study Type: interventional
• Target: 81
• Locations: 6 countries
• Sites: 11

Brief Summary

The aim of this randomized, double-blind, placebo-controlled, phase 2b clinical trial is to investigate the safety and efficacy of GH001 (containing mebufotenin \[5-methoxy-N,N-dimethyltryptamine; 5-MeO-DMT\]) in patients with treatment-resistant depression (TRD). The study is comprised of a 7-day double-blind (DB) part (Part 1) and a 6-month open-label extension (OLE) part (Part 2). Patients will be randomized to receive GH001 or placebo in a 1:1 ratio. The primary endpoint is the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to Day 7.

Conditions

Treatment-resistant Depression

Keywords

Treatment-resistant depression; Major depressive disorder; Depression; GH001; 5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine; Mebufotenin

Outcome Measures

Primary Outcomes (1)

• Mean change in MADRS from Baseline to Day 7

  The assessment is done with the MADRS, a diagnostic questionnaire with ten items for measuring the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item is scored from 0 to 6. The overall score ranges from 0 to 60.

  Baseline to Day 7

Study Arms (3)

GH001 - Part 1

EXPERIMENTAL

GH001 is administered via inhalation, as an IDR consisting of up to 3 increasing doses of GH001 (6 mg, 12 mg, and 18 mg), on a single day. The second and third doses are only administered if the patient did not achieve intense psychoactive effects (a peak experience \[PE\]) at the previously administered dose.

Drug: GH001

Placebo - Part 1

PLACEBO COMPARATOR

Placebo is administered via inhalation, as an IDR consisting of up to 3 doses of Placebo, on a single day. The second and third doses are only administered if the patient did not achieve intense psychoactive effects (a PE) at the previously administered dose.

Drug: Placebo

Open-Label Extension (OLE) - Part 2

OTHER

Patients can receive up to five GH001 IDRs as needed during the OLE based on the patient's clinical response.

Drug: GH001

Interventions

GH001 DRUG

GH001 administered via inhalation

Also known as: 5-Methoxy-N,N-dimethyltryptamine, 5-MeO-DMT, Mebufotenin

GH001 - Part 1; Open-Label Extension (OLE) - Part 2

Placebo DRUG

Placebo administered via inhalation

Placebo - Part 1

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Is in the age range between 18 and 64 years (inclusive) at the time of informed consent;
• Meets the trial criteria for TRD as assessed by a study psychiatrist:
• Meets the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features confirmed by the Mini-International Neuropsychiatric Interview (MINI) with current episode duration of ≤2 years;
• The current major depressive episode must be deemed "valid" based upon the Massachusetts General Hospital State versus trait Assessability Face and Ecological validity Rule of 3Ps (MGH SAFER) criteria interview;
• Had nonresponse (≤25% improvement) to ≥2 and ≤5 oral antidepressant treatments administered during the current episode of depression.

You may not qualify if:

• Has, based on history, psychiatric assessment, and evaluation of the MINI during the screening period, a first MDD episode after age 60, a current or prior diagnosis of a psychotic disorder, MDD, or other mood disorder with psychotic features, bipolar disorder, obsessive compulsive disorder, posttraumatic stress disorder, autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disability, antisocial personality disorder, schizotypal personality disorder, or any other psychiatric comorbidity that renders the patient unsuitable for the trial according to a study psychiatrist;
• Has significant suicide risk;
• Has 1 or more first degree relatives with a current or prior diagnosis of bipolar disorder, psychotic disorder, or other mood disorder (including MDD) with psychotic features;
• Undergoing systematic psychotherapy that is planned to be modified or planning to initiate psychotherapy during the trial;
• Has any current or past clinically significant condition that may interfere with the interpretation of the trial results, constitute a health risk for the patient, or that otherwise renders the patient unsuitable for the trial according to the investigator's judgement;
• Fulfils criteria for DSM-5 alcohol or substance use disorder (excluding tobacco and caffeine use disorders) within the preceding 1 year, as assessed via the MINI;
• Is taking antidepressants, antipsychotics, or any medication with monoamine oxidase inhibitors activity or takes or has taken other disallowed recent or concomitant treatments or it is anticipated that the patient will require treatment with at least 1 of the disallowed concomitant treatments during the trial;
• Has previously experienced a significant adverse reaction to a hallucinogenic or psychedelic drug (e.g., psilocybin, Psilocybe spp. mushrooms, 5-MeO-DMT, DMT, ayahuasca, lysergic acid diethylamide, mescaline) according to the investigator's judgement.

Sponsors & Collaborators

• GH Research Ireland Limited: lead

Study Sites (11)

Investigational site

Pilsen, Czechia

Location

Investigational site

Prague, Czechia

Location

Investigational Site

Dresden, Germany

Location

Investigational Site

Frankfurt, Germany

Location

Investigational Site

Münster, Germany

Location

Investigational site

Dublin, Ireland

Location

Investigational Site

Galway, Ireland

Location

Investigational Site

Maastricht, Netherlands

Location

Investigational Site

Gdansk, Poland

Location

Investigational Site

Barcelona, Spain

Location

Investigational Site

Salamanca, Spain

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Depression

Interventions

Methoxydimethyltryptamines

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

N,N-Dimethyltryptamine; Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Bufotenin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Serotonin

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 6, 2023
• Study Start: May 24, 2023
• Primary Completion: October 4, 2024
• Study Completion: March 11, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); ES (2); DE (3); CZ (2); NL (1); IE (2)